The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation and pruritus.

Aspirin may increase the likelihood of hemorrhage due to its effect on the gastric mucosa and platelet function. Furthermore, aspirin has the potential to cause anaphylaxis in hypersensitive patients as well as angioedema especially in patients with chronic urticaria. Other adverse reactions due to aspirin use include anorexia, reversible hepatotoxicity, leukopenia, thrombocytopenia, purpura, decreased plasma iron concentration, and shortened erythrocyte survival time.

Other adverse reactions obtained from postmarketing experiences with PERCODAN (aspirin and oxycodone hydrochloride) tablets are listed by organ system and in decreasing order of severity and/or frequency as follows:

DRUG INTERACTIONS

Drug/Drug Interactions with Oxycodone

CYP3A4 Inhibitors and CYP450 Inducers

Oxycodone is extensively metabolized by multiple metabolic pathways. CYP3A4 is the major enzyme involved in noroxycodone formation followed by CYP2B6, CYP2C9/19 and CYP2D6. Drugs that inhibit CYP3A4 activity, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations and prolonged opioid effects. Similarly, CYP450 inducers, such as rifampin, carbamazepine, and phenytoin, may induce the metabolism of oxycodone and, therefore, may cause increased clearance of the drug which could lead to a decrease in oxycodone plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone.

If co-administration with PERCODAN (aspirin and oxycodone hydrochloride) is necessary, caution is advised when initiating therapy with, currently taking, or discontinuing CYP3A4 inhibitors or CYP450 inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved.

Skeletal Muscle Relaxants

Opioid analgesics may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.

CNS Depressants

Patients receiving CNS depressants such as other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with PERCODAN (aspirin and oxycodone hydrochloride) tablets may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

Analgesics

Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, and butorphanol) should be administered with caution to a patient who has received or is receiving a pure opioid agonist such as oxycodone. These agonist/antagonist analgesics may reduce the analgesic effect of oxycodone or may precipitate withdrawal symptoms.

Drug/Drug Interactions with Aspirin

Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration
of aspirin due to its indirect effect on the renin-angiotensin conversion pathway.

Acetazolamide: Concurrent use of aspirin and acetazolamide can lead
to high serum concentrations of acetazolamide (and toxicity) due to competition
at the renal tubule for secretion.

Anticoagulant Therapy (Heparin and Warfarin): Patients on anticoagulation
therapy are at increased risk for bleeding because of drug-drug interactions
and the effect on platelets. Aspirin can displace warfarin from protein binding
sites, leading to prolongation of both the prothrombin time and the bleeding
time. Aspirin can increase the anticoagulant activity of heparin, increasing
bleeding risk.

Anticonvulsants: Salicylate can displace protein-bound phenytoin and
valproic acid, leading to a decrease in the total concentration of phenytoin
and an increase in serum valproic acid levels.

Beta Blockers: The hypotensive effects of beta blockers may be diminished
by the concomitant administration of aspirin due to inhibition of renal prostaglandins,
leading to decreased renal blood flow, and salt and fluid retention.

Diuretics: The effectiveness of diuretics in patients with underlying
renal or cardiovascular disease may be diminished by the concomitant administration
of aspirin due to inhibition of renal prostaglandins, leading to decreased renal
blood flow and salt and fluid retention.

Methotrexate: Aspirin may enhance the serious side and toxicity of methotrexate
due to displacement from its plasma protein binding sites and/or reduced renal
clearance.

Nonsteroidal Anti-inflammatory Drugs (NSAID's): The concurrent use of
aspirin with other NSAID's should be avoided because this may increase bleeding
or lead to decreased renal function. Aspirin may enhance the serious side effects
and toxicity of ketorolac, due to displacement from its plasma protein binding
sites and/or reduced renal clearance.

Oral Hypoglycemics Agents: Aspirin may increase the serum glucose-lowering
action of insulin and sulfonylureas leading to hypoglycemia.

Drug/Laboratory Test Interactions

Depending on the sensitivity/specificity and the test methodology, the individual components of PERCODAN (aspirin and oxycodone hydrochloride) tablets may cross-react with assays used in the preliminary detection of cocaine (primary urinary metabolite, benzoylecgonine) or marijuana (cannabinoids) in human urine. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. The preferred confirmatory method is gas chromatography/mass spectrometry (GC/MS). Moreover, clinical considerations and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

Salicylates may increase the protein bound iodine (FBI) result by competing for the protein binding sites on pre-albumin and possibly thyroid-binding globulins.

Drug Abuse And Dependence

PERCODAN (aspirin and oxycodone hydrochloride) tablets are a Schedule II controlled substance. Oxycodone is a mu-agonist opioid with an abuse liability similar to morphine. Oxycodone, like morphine and other opioids used in analgesia, can be abused and is subject to criminal diversion.

Drug addiction is defined as an abnormal, compulsive use, use for non-medical purposes of a substance despite physical, psychological, occupational or interpersonal difficulties resulting from such use, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common. Opioid addiction is relatively rare in patients with chronic pain but may be more common in individuals who have a past history of alcohol or substance abuse or dependence. Pseudoaddiction refers to pain relief seeking behavior of patients whose pain is poorly managed. It is considered an iatrogenic effect of ineffective pain management. The health care provider must assess continuously the psychological and clinical condition of a pain patient in order to distinguish addiction from pseudoaddiction and thus, be able to treat the pain adequately.

Physical dependence on a prescribed medication does not signify addiction. Physical dependence involves the occurrence of a withdrawal syndrome when there is sudden reduction or cessation in drug use or if an opiate antagonist is administered. Physical dependence can be detected after a few days of opioid therapy. However, clinically significant physical dependence is only seen after several weeks of relatively high dosage therapy. In this case, abrupt discontinuation of the opioid may result in a withdrawal syndrome. If the discontinuation of opioids is therapeutically indicated, gradual tapering of the drug over a 2-week period will prevent withdrawal symptoms. The severity of the withdrawal syndrome depends primarily on the daily dosage of the opioid, the duration of therapy and medical status of the individual.

"Drug-seeking" behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated "loss" of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). "Doctor shopping" to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Oxycodone, like other opioids, has been diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Like other opioid medications, PERCODAN (aspirin and oxycodone hydrochloride) tablets are subject to the Federal Controlled Substances Act. After chronic use, PERCODAN (aspirin and oxycodone hydrochloride) tablets should not be discontinued abruptly when it is thought that the patient has become physically dependent on oxycodone.

Interactions with Alcohol and Drugs of Abuse

Oxycodone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

Last reviewed on RxList: 8/12/2010
This monograph has been modified to include the generic and brand name in many instances.